The objective of this project is to raise and characterize an antibody directed against the combining site of a T lymphocyte receptor for a cell surface antigen. Such an antireceptor antibody will be used to establish a murine model for studying the genetics and cellular interactions involved in the cellular immune response to tumor antigens and transplantation antigens. Cloned cytotoxic T lymphocytes will be used for immunization and as a target for assaying the antibody. The cytotoxic cells will be generated to recognize the difference between a mouse strain and a histoincompatible strain differing from the first only in a point mutation. The principal criterion of receptor specificity of the antibody produced will be preferential activity after appropriate absorptions for cytotoxic cells of the original specificity. The antibody will be used to test the following hypotheses: (1) the combining site is genetically determined and linked to the major histocompatibility complex or to IgG heavy chain allotype, (2) the same combining site is found on both B and T cells, (3) the combining site can be detected in animals expressing the antigen with which the combining site interacts, (4) the antibody can induce an antigen specific immune response in the absence of antigen or suppress the immunoresponse to antigen. These hypotheses bear in fundamentally important ways on the specific interactions of the immune response with tumor antigens and transplantation antigens and would lead to predictions concerning clinically useful manipulations of the immune response to these antigens.